Oxytocin was one of the first peptide hormones to be isolated and sequenced. It is a nonapeptide with two cysteine residues that form a disulfide bridge between positions 1 and 6 and corresponds to the formula

For a long time the only effects attributed to oxytocin were its stimulating effects on milk ejection and uterine contractions, but in the past decades it has been shown that oxytocin exerts a wide spectrum of effects within the central nervous system, CNS. It has been suggested that oxytocin participates in the control of memory and learning processes and of various types of behaviour such as feeding, locomotion, as well as maternal and sexual behaviour. Oxytocin is also suggested to participate in the control of cardiovascular functions, thermoregulation, and pain threshold and fluid balance. There is also evidence that oxytocin is involved in the control of various immunological processes. It has recently been demonstrated that oxytocin injections cause a lowering of blood pressure and increased weight gain—long lasting effects after repetitive administration. As a central stimulating substance oxytocin plays an important role in the interaction between mother and progeny in mammals. The products may also be used prophylactic in young human beings e.g. already in new born babies or young children to prevent the development of diseases later on in life which diseases are dependent on stress conditions during the fetal life. Such conditions may be heart/vessel diseases such as stroke, heart infarct, hypertension, and diabetes.
In the human body oxytocin is produced in the paraventricular nucleus, PVN, and the supraoptic nucleus, SON, of the hypothalamus. It differs by only two amino acids from vasopressin, which is also produced in these nuclei. The magnocellular oxytocinergic neurones of the SON and PVN send oxons to the posterior pituitary from which oxytocin is released into the circulation. Parvocellular neurones that originate in the PVN project into multiple areas within CNS. The oxytocin-producing cells are innervated by cholinergic, catecholaminergic as well as peptidergic neurones. The presence of oxytocin in different tissues outside the brain, such as the uterus, ovaries, testis, thymus, adrenal medulla and pancreas has been demonstrated and oxytocin is suggested to exert local effects in these organs.
A parallel secretion of oxytocin into the brain regions and into the circulation occurs in response to some stimuli such as suckling, but other stimuli can cause separate activation of oxytocinergic neurones, terminating in the brain or the pituitary.
It has now turned out that oxytocin has a relieving effect on climacteric disorders.
There are several oxytocin derivatives, i.e. compounds with a structure similar to that of oxytocin. The inventors have preliminary indications that other oxytocin derivatives than oxytocin could give the effects against climacteric disorders and disorders of ovarian functions as well as parts of the oxytocin molecule. No publications describe the use of oxytocin or any other oxytocin derivatives or parts of the oxytocin molecule to have effects against climacteric disorders or other types of premature ovarian dysfunction.
By the expression “climacteric disorders” we understand premenopausal (i e before the menopause), perimenopausal (i e during the menopause) and postmenopausal (i e after the menopause) weight changes, mood swings, hot flushes (transient redness and a feeling of being warm), somatic discomfort, dry and ulcerous mucous membranes, fissures, and bone loss. Such symptoms often occur at the time of the menopause, i e the cessation of menstruation in the human female, occurring usually around the age of 50.
It has now turned out that oxytocin improves the vaginal mucosal membranes of women with postmenopausal disorders and improves the mood of such women (Example 1). In an animal model of menopause, i.e. ovariectomy, oxytocin normalises hormone levels and moderates weight changes (Example 2), increases motor activity and relieves somatic discomfort (Example 3), reduces hot flushes (Example 4), reduces hyperactivity in the sympathetic nervous system (Example 5), and suppresses bone loss (Example 6). These Examples indicate that oxytocin or that substances with oxytocin activity may be used against climacteric disorders and ovarian dysfunction. The oxytocin derivatives according to the invention are not only suitable against postmenopausal disorders but also against premenopausal, perimenopausal and ovarian dysfunction.
The effect of oxytocin can be extended or strengthened by administration in combination with drugs increasing the release of oxytocin and/or the number or affinity of receptors, such as oestrogen, or drugs having an α2-agonistic effect, such as clonidine.